DESCRIPTION (Applicant's Abstract): We will investigate mechanisms involved in the incorporation of drugs of abuse into human hair. The pharmacokinetics of cocaine and methamphetamine in hair, skin, sweat and sebum, and plasma will be characterized so as to better understand mechanisms by which drugs enter hair. Multiple mechanisms and pathways involving skin tissues and skin secretions as possible reservoirs and transport vehicles for drugs will be considered. Skin is sometimes considered to be the largest organ of the body. Dose and time dependent concentrations, time course of uptake and disappearance, apparent partition coefficients and the relationships between the skin concentrations of drugs and major metabolites in various biofluid and tissue samples will be determined. We will determine how significant are sweat and sebaceous gland secretions for incorporation of drugs into hair and examine hair color and racial differences in the uptake of drugs into hair. Deuterium-labeled cocaine and methamphetamine will be administered to human volunteers and sequential plasma, urine, skin, sweat, and hair samples will be analyzed by gas chroma-tography and mass spectrometry. Drug and metabolite concentrations will be measured in skin punch biopsy specimens, stratum corneum, interstitial fluid, sebum, sweat and hair. Relationships between dose and the skin concentrations, skin pharmacological responses and hair levels will be determined. From these data, we will model the role of skin tissues and skin secretions in the transport of drugs into hair and sweat. The use of isotope-labeled drugs to control for residual stores of the drug in the body and surreptitious drug use by subjects will allow many months of outpatient study after a single dose given in a laboratory setting since illicit use of the labeled test drug will not interfere with following the course of the test dose. The research will provide useful scientific information for interpretation of hair and sweat and hair analysis as a biomarker for exposure to drugs and chemicals.